J. Am. Chem. SOC.1995,117, 12306-12313
12306
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Substituent and Solvent Effects in the [2 21 Cycloaddition Reaction between Olefins and Isocyanates Fernando P. Cessio,*" Guillermo RoaJ Begoiia Lecea? and Jesus M, Ugalde? Contribution ffom the Kimika Fakultatea, Euskal Herriko Unibertsitatea, P.K. 1072, 20080 San Sebastibn-Donostia, Spain, and Farmazi Fakultatea, Euskal Herriko Unibertsitatea, P.K. 450, 01080 Vitoria-Gasteiz, Spain Received April 19, 1995"
Abstract: Ab initio calculations provide with the models to explain the main features of the cycloaddition between olefins and isocyanates to yield 2-azetidinones (B-lactams). It is found that the reaction takes place via concerted transition structures involving retention of configuration in the starting olefins. These transition structures have zwitterionic character. The presence of olefins having n-donating groups andor isocyanates with electron-withdrawing groups diminish the synchronicity as well as the activation energy of the reaction, yielding exclusively the 4-substituted regioisomers. The solvent enhances the asynchronicity of the reaction and can modify its profile from a concerted to a two-step process, thus explaining the loss of stereospecificityobserved in the reaction between sulfonyl isocyanates and vinyl ethers.
Scheme 1"
Introduction One of the most general methods to synthesize 2-azetidinone rings (p-lactams) in a convergent fashion consists in the cycloaddition reaction between alkenes and isocyanates' (Scheme 1). Similarly, the interaction between allenes and isocyanates provide a general access to a-alkylidene-/3-lactams.*The practical importance of this reaction is due to its usefulness in the chemical synthesis of p-lactam antibiotics, mainly carbapenem compound^.^ Thus, the cycloaddition between isocyanates and alkenes has been successfully applied to the synthesis of antibiotics such as PS-5: PS-6,5thienamycin,6 and I/?-methylcarbapenems.' Similarly, the reaction of isocyanates and allenes provides useful building blocks for the synthesis of carpetimycinss and asparenomy~ins.~ Kimika Fakultatea. Farmazi Fakultatea. Abstract published in Advance ACS Abstracts, November 15, 1995. (1) (a) Grai, R. Ann. 1963,661, 111. (b) Hoffmann, H.; Diehr, H. J. Tetrahedron Lett. 1963,1875. (c) Friedrich, H. J. Tetrahedron Lett. 1971, 2981. (d) Clauss, K. Ann. 1969,722, 110. (2) (a) Moriconi, E. J.; Kelly, J. F. J. Am. Chem. SOC. 1986,88, 3657. (b) Buynak, J. D.; Rao, M. N. J. Org. Chem. 1986,51, 1571. (c) Buynak, J. D.; Mathew, J.; Rao, M. N.; Haley, E.; George, C.; Siriwardane, V. J. Chem. Soc., Chem. Commun. 1987,735. (3) (a) Chemistry and Biology of P-Lactam Antibiotics; Morin, R. B., Gorman, M., Eds.; Academic Press: New York, 1982; Vols 1-3. (b) Kametani, T.; Fukumoto, K.; Imara, M. Heterocycles 1982, 17,463. (c) Nagahara, T.; Kametani, T. Heterocycles 1987,25,729.(d) Recent Progress in the Chemical Synthesis of Antibiotics; Lukacs, G., Ohno, M., Eds.; Springer-Verlag, Berlin, 1990; pp 562-612. (4) (a) Kametani, T.; Honda, T.; Nakayama, A.; Fukumoto, K. Heterocycles 1982,14, 1967. (b) Bateson, J. H.; Hickling, R. I.; Roberts, P. M.; Smale, T. C.; Southgate, R. J. Chem. SOC., Chem. Commun. 1980,1084. (c) Wasserman, H. H.; Han, T. Tetrahedron Lett. 1984,25,3747.(d) Favara, D.; Omodei-Salk, A.; Consonni, P.; Depaoli, A. Tetrahedron Lett. 1982, 23,3105. (5) Kametani, T.; Honda, T.; Nakayama, A,; Sasakai, Y.; Mochizuki, T.; Fukumoto, K. J. Chem. SOC., Perkin Trans. I1981,2228. (6) (a) Meyers, A. I.; Sowin, T. J.; Scholz, S.; Ueda, Y. Tetrahedron Lett. 1987,28, 5103. (b) Johnston, D. B. R.; Schmitt, S . M.; Bouffard, F. A.; Christensen, B. G. J. Am. Chem. SOC. 1978,100, 30. (c) Buynak, J. D.; Mathew, J.; Rao, M. N. J. Chem. Soc., Chem. Commun. 1986,941. (d) Ohashi, T.; Kan, K.; Sada, I.; Miyama, A,; Watanabe, K. Eur. f a t . Appl. 1986,167155 (Chem. Abstracts 1986,105, 60469). (7) Kobayashi, Y.; Ito, Y.; Terashima, S. Tetrahedron 1992,48, 55. (8) Buynak, J. D.; Rao, M. N. J. 0rg.Chem. 1986,51, 1571. (9) Buynak, J. D.; Rao, M. N.; Pajouhesh, H.; Chandrasekaran, R. Y.; Finn, K. J. Org. Chem. 1985,50, 4245. @
O==N
\I+9 *
N ,
0 The possible substituents at the different positions are not specified.
The main features and the scope of these cycloadditions have been reviewed.I0 From the experimental evidence available, the following observations emerge. (i) The Presence of Electron-Withdrawing Groups in the kocyanates Facilitates the Reaction. In particular, the isocyanates commonly employed in this reaction incorporate acyl and sulfonyl groups." In this respect the most versatile reagent is chlorosulfonyl isocyanate (CSI).'* Isocyanates without electron-withdrawing groups only react with electron-rich olefins, such as enamines13 or ketene acetals.Iob (ii) Olefins with Electron-Donating Substituents React Readily Yielding Markovnikov Regioisomers. Thus, the reaction of chlorosulfonyl isocyanate with a-olefins such as allyl iodideI4 or vinyl acetatet5 yields exclusively the 4-substituted (10) (a) Mukerjee, A. K.; Srivastava, R. C. Synthesis 1973, 32. (b) Ghosez, L.; Marchand-Brynaert, J. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 5, pp 85122. (c) Oligaxuso, M. A.; Wolfe, J. F. In Synthesis ofkctones andLuctams; Patai, S.,Rappoport, Z., Eds.; Wiley: Chichester, 1993; pp 162-168,475489. (11) (a) Arbuzov, B. A,; Zobova, N. N. Synthesis 1974,461. (b) Tsuge, 0'.Heterocycles 1979,12,1067. (c) Arbuzov, B. A,; Zobova, N. N. Synthesis 1982,433. (d) Bmett, A. G. M.; Betts, M. J.; Fenwick; A. J. Org. Chem. 1985,50, 169. (12) (a) Graf, R. Angew. Chem., Int. Ed. Engl. 1968,7, 172. (b) Bestian, H. Pure Appl. Chem. 1971,27, 611. (c) Rasmussen, J. K.; Hassner, A. Chem. Rev. 1976,76, 389. (d) Szabo, W. A. Aldrich. Acta 1977,IO, 23. (e) Nathdhar, D.; Murthy, K. S. K. Synthesis 1986,437. ( f ) Reichardt, C. Solvents and Solvent Effects in Organic Chemistry; VCH: Weinheim, 1990; pp 155-156. (13) (a) Hickmott, P. W. Tetrahedron 1982,38, 1975. (b) Hickmott, P. W. Tetrahedron 1982,3,3363.
0002-786319511517-12306$09.00/00 1995 American Chemical Society
[2
+ 21 Cycloaddition Reaction between Olefins and Isocyanate
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J. Am. Chem. SOC.,Vol. 117, No. 49, I995 12307
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cycloadducts. Other substituted alkenes behave similarly.1o the Wo~dward-Hoffmann~~ rules for [2 21 thermal cycloWhen the reaction is carried out with 1,Zdisubstituted olefins additions. Finally, Huysgen28 and other^^^^^^ have proposed concerted, although asynchronous, transition states of type D incorporating groups with comparable donating ability, variable mixtures of the two possible regioisomers are obtained.I6 (Figure 1) to account for their experimental results. However, the reasons underlying these non-Woodward-Hoffmann ge(iii) 1,2-Disubstituted Alkenes React with Retention of ometries were not explained, although a possible participation Configuration. This stereochemical outcome has been obof d-orbitals of sulfur atoms in sulfonyl isocyanates was served with dialky1I6,l7or a l k ~ l a r y l olefins. ’~ Similarly, cyclic sugge~ted.~~.~~ alkenesI6.I8yield the corresponding cis cycloadducts. Differently substituted norbomenes react via the ex0 f a ~ e . ~ ~ ~.In- ~view ~ of these precedents, and as part of our research program devoted to the study of [2 21 cycloadditions between However, one exception has been reported. In 1967, Effencumulenes and double bond^,^^,^^ we report here our results on berger and Kiefer20a observed that trans- 1-butenyl ethyl ether the reaction between isocyanates and olefins to form 2-azetireacts with p-tosyl isocyanate to yield exclusively the corredinones. Our purpose has been to understand the origins of By contrast, cissponding trans-4-ethoxy-3-ethylazetidin-2-one. the regio- and stereocontrol observed in this reaction as well as 1-butenyl ethyl ether forms fiistly the corresponding cisto clarify whether one or several mechanisms are involved. cycloadduct, but this compound epimerizes under the reaction conditions to form predominantly the thermodynamically more stable trans-/3-lactam. (After 1440 min of reaction time, the Computational Methods cisltrans ratio is 27:73.) Some years later, Effenberger et aL20b All the results presented in this work have been obtained using ab reported a kinetic study on the epimerization of 4-alkoxy-linitio MO theory, by means of the GAUSSIAN 92 series of programs,3’ tosylazetidin-2-ones. with the standard 6-31G* and 6-31+G* basis sets.32 Geometry (iv) Polar Solvents Accelerate the Reaction Rates.lZc For optimizations have been carried out at the HF/6-31G* level, and some example, it has been reported12fthat in the [2 21 cycloaddition representative structures have also been optimized at the MP2/6-3 1+G* level of theory. No symmetry constrains were imposed during the between CSI and 2-ethyl-1-hexene the rate acceleration in optimizations. The energies have been then recalculated at the MP2/ dichloromethane with respect to n-hexane is k2(CH2Cl&(n6-31G* keeping the core electrons frozen. In some cases, C6H14) = 1700. This result suggests the participation of single-point energies at MP3/6-3 1+G* and MP4SDQ/6-3 1+G* levels zwitterionic intermediates or highly polar transition states in have also been computed. HF/6-3 1G* zero-point vibrational energies34 the mechanism of the reaction. (ZPVE) have been scaled3s by 0.89. Stationary points were characterIn spite of the practical importance of the reaction and ized by frequency calculation^.^^ All reactants, intermediates, and theoretical interest of thermal [2 21 cycloadditions,21 this products have positive defined Hessian matrices. Transition structures (TS’s) showed only one negative eigenvalue in their diagonalized force process has not been investigated using modem high-level constant matrices, and their associated eigenvectors were confirmed computational tools, with the exception of a preliminary to correspond to the motion along the reaction coordinate under communication reported by our group.22 Instead, qualitative consideration. Atomic charges3’ were calculated with the natural concerted or stepwise models have been proposed in order to bonding analysis (NBA) method.38 account for diverse experimental observations. The key interSolvent effects have been computed using a self-consistent reaction mediates or transition structures corresponding to these models field (SCRF) method39based on the procedures developed by Rinaldi, have been collected in Figure 1. Thus, G d 3 proposed a twostep mechanism involving the participation of zwitterionic (27) Woodward, R. B.; Hoffmann, R. Angew. Chem., Int. Ed. Engl. 1969, intermediates A. Since then, these intermediates have been 8, 781. (28) See footnote 13 in ref 25. assumed to explain diverse epimerizations20 and rearrangements (29) Chmielewsky, M.; Kaluza, Z.; Belzecki, C.; Salanski, P.; Jurczak, observed in the reaction between electrophilic isocyanates and J.; Adamowicz, H. Tetrahedron 1985, 41, 2441. various conjugated olefins.24 The total stereocontrol usually (30) (a) Cossio, F. P.; Ugalde, J. M.; Lopez, X.; Lecea, B.; Palomo, C. J. Am. Chem. SOC. 1993,115, 995. (b) Cossio, F. P.; Ameta, A,; Lecea, B.; observed can be explained assuming a fast collapse between Ugalde, J. M. J. Am. Chem. SOC. 1994, 116, 2085. (c) Lecea, B.; Anieta, the N(l) and C(4) atoms of the zwitterionic intermediate, via A.; Roa, G.; Ugalde, J. M.; Cossio, F. P. J. Am. Chem. SOC. 1994, 116, transition states of type B25(Figure 1). On the other hand, in 9613. (31) Gaussian 92, Revision C.; Frisch, M. J.; Trucks, G. W.; Headthe course of his study on the thermolysis of several p-lactams Gordon, M.; Gill, P. M. W.; Wong, M. W.; Foresman, J. B.; Johnson, B. to yield olefins and isocyanates, Paquette26suggested a concerted G.; Schlegel, H. B.; Robb, M. A.; Replogle, E. S.;Gomperts, R.; Andres, supra-antara transition state of type C (Figure l), in line with J. L.; Raghavachk, K.; Binkley, J. S.; Gonzalez, C.; Martin, R. L.; Fox,
+
+
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(14) Tanaka T.; Miyadera, T. Heterocycles 1982, 19, 1497. (15) Hauser, F. M; Ellenberger, S. R. Synthesis 1987, 324. (16) Bestian, H.; Biener, M.; Clauss, K.; Heyn, H. Ann. 1968, 718, 94. (17) Moriconi, E. J.; Meyer, W. C. J. 0rg.Chem. 1971, 36, 2841. (18) (a) Durst, T.; O’Sullivan, M. J. J. 0rg.Chem. 1979, 35, 2043. (b) Moriconi, E. J.; Mazzochi, P. H. J. 0rg.Chem. 1966, 31, 1372. (19) Moriconi, E. J.; Crawford, W. C. J. Org. Chem. 1968, 33, 370. (20) (a) Effenberger, F.; Kiefer, G. Angew. Chem., Inf. Ed. Engl. 1967, 6 , 951. (b) Effenberger, F.; Prossel, G.; Fischer, P. Chem. Ber. 1971, 104, 2002. (21) Houk, K. N.; Li, Y.; Evanseck, J. D. Angew. Chem., Inr. Ed. Engl. 1992, 31, 682. (22) Cossio, F. P.; Lecea, B.; Lopez, X.; Roa, G.; Ameta, A,; Ugalde, J. M. J. Chem. SOC.,Chem. Commun. 1993, 1450. (23)Graf, R. Chem. Ber. 1956, 89, 1071. (24) (a) Barton, T. J.; Rogido, R. J. Tetrahedron Lett. 1972, 3901. (b) Malpass, J. R. Chem. Commun. 1972, 1246. (c) Malpass, J. R.; Tweddle, N. J. Chem. Commun. 1972, 1244. (d) Malpass, J. R.; Tweddle, N. J. Chem. Commun. 1972, 1247. ( 2 5 ) Monconi, E. J.; Kelly, J. F. Tetrahedron Left 1968, 1435. (26) Paquette, L. A.; Kakihana, T.; Hansen, J. F.; Philips, J. C. J . Am. Chem. SOC. 1971, 93, 152.
D. J.; Defrees, D. J.; Baker, J.; Stewart, J. J. P.; Pople, J. A. Gaussian, Inc.: Pittsburgh PA, 1992. (32) (a) Hariharan. P. C.; Pople, J. A. Chem. Phys. Lett. 1972, 66, 217. (b) Francl, M. M.; Pietro, W. J.; Hehre, W. J.; Binkley, J. S.; Gordon, M. S.; DeFrees, D. J.; Pople, J. A. J. Chem. Phys. 1982, 77, 3654. (c) Clark, T.; Chandrasekhar, J.; Spitznagel, G. W.; Schleyer, P. v. R. J. Comput. Chem. 1983,4, 294. (d) Frisch, M. J.; Pople, J. A,; Binkley, J. S. J. Chem. Phys. 1994, 80, 3265. (33) (a) Binkley, J. S.; Pople, J. A. Int. J. Quantum Chem. 1975, 9, 229. (b) Pople, J. A.; Binkley, J. S.; Seeger, R. Int. J. Quantum Chem. Symp. 1976, 10, 1. (34) Hehre, W. J.; Radom, L.; Schleyer, P. v. R.; Pople, J. A. In Ab Initio Molecular Orbital Theory; Wiley: New York, 1986. (35) Pople, J. A.; Schlegel, B.; Krishnan, R.; DeFrees, D. J.; Binkley, J. S.; Frisch, H.; Whitheside, R.; Hout, R. F., Jr.; Hehre, W. J. Inr. J. Quantum Chem. Symp. 1981, 15, 269. (36)McIver, J. W.; Komomicki, A. K. J. Am. Chem. SOC.1972, 94, 2625. (37) Wiberg, K. B.; Rabien, P. R. J. Comput. Chem. 1993, 14, 1504. (38) (a) Reed, A. E.; Weinstock, R. B.; Weinhold, F. J. Chem. Phys. 1985, 83, 735. (b) Reed, A. E.; Curtiss, L. A.; Weinhold, F. Chem. Rev. 1988.88, 899. (c) Reed, A. E.; Schleyer, P. v. R. J. Am. Chem. SOC. 1990, 112, 1434.
12308 J. Am. Chem. Soc.. Vol. 117, No. 49, 1995
Cossio
et
a/.
Scheme 2 o = Nl-C2-C3-Cn
A
0
C
D
Figure 1. Transition structures and intermediates previously proposed in the cycloaddition reaction hetween alkenes and isocyanates. The possihle suhstituents at the different positions are not specified.
Rivail P I d."'The calculations have heen carried out with a locally modified version of the GAUSSIAN 92 program suite. to incorporate the SCRFPAC link." This program includes estimates of the cavitation and dispersion energies as well as the electrosiatic free energy of solvation for an ellipsoidal cavity. defined frnm the geometry of the snlute and a multipole expansion of the energy. computed at the center of the cavity."'""' This methodology has been used successfully for the study of diverse cycloaddition reactions.""?
Results and Discussion
+
General Considerations. If we assume that the [2 21 cycloaddition between alkenes and isocyanates is a concerted reaction, then two alternative mechanisms can he envisaged. One possibility is the classical [.,2,+,72,] mechanism (Figure I , structure C) or, in a more elaborated form, a [,2,+(,2,+,2,)] 21 interaction mode, as it has been described for the [2 cycloaddition between alkenes and cumulenes such as allenesl? or If we denote the dihedral angle between N(I), C(2). (231, and C(4) atoms as w , it is clear that the [,2,+(,2,+,2,)] geometry at the TS implies a value of w different from zero (see structure E in Scheme 2). In addition, the degree of advancement of the N(I)-C(4) bond should he lower than bonding between the C(2) and C(3) atoms, because of the more favorable overlap in the latter case (Scheme 2). An alternative mechanism consists in a push-pull interaction between the lone pair of the isocyanate, the nucleophilic mof the alkene, and the electrophilic nco* of the isocyanate. A similar mechanism could he also adscribed to the uncatalyzed thermolysis of p-lactones to yield alkenes and carbon dioxide.?h As it can be appreciated looking at the Structure D in Scheme ..
+
I
( 2 9 ) (a1 Tomnsi. J.: Bonaccorsi. R.: Cammi, R.: Oliviires del Valle. F. J . J. U o l . Stnu'r. (Tl?uorlternj 1991. 234. 401. lh) Tomasi. J.: Pemico. M.Clwm. nli.. 1994.94. 2027. (40) (a) Rinnldi. D.: Rivail. 1. L.: Rguini. N. J. Compul. Clwm. 1992, I.?. h75. ih) Rinaldi. D. J . C,unIm Clwm 1982. 6. 155. IC) Rmaldi. D.: Ruir-L6pez. M . F.: Rivnil. J . L. I . Cltrm. P I y t 1983. 7X. 834. (41) Rinaldi. D.: Pappalardo. R. R. S C R P A C Quantum Chemistry Program Exchange. Indiana Universiry: Bloomingron. IN. 1992: program Nu. 622. (42) See. for example: i a ) Assfeld. X.: Sordo. J. A.: Gondler, I.: RuirLilper. M. F.: Sordo. T. L. J . Mol. Cwurr. ITI~eorh~~mJ 1993.287, 193. ( h ) Ruii-Ldper. M. F.: Assfeld. X.: Garcia. J. I.: Mayoral. J. A,: Salvarella. L. J . A m CBrrtt. Sot. 1993, 115, 8780. (c) Assfeld. X.: Ruiz-L6pez. M. F.: Garcis. 1. I.: Mayoral. I. A,: Salvatellil. L. J. Chem. Soc., C h ~ nCmnmtm. . 1995 .. ... 1371 .. . ., (43) Parr". D. J . J. A m Chrm .So
